反应详情

Into a 100 mL round bottom flask equipped with a nitrogen inlet and magnetic stirrer is added 327 mg (0.89 mmol, 1.0 equiv.) of 6-Methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-4H-chromene-2-carboxylic acid hydrochloride salt (Reference Example 23). This material is dissolved in 20 mL of DMF and then 189 mg (1.06 mmol, 1.2 equiv.) of 4-morpholinoaniline is added. To the stirred solution is quickly added simultaneously added 568 mg (1.77 mmol, 2.0 equiv.) of TBTU and 239 mg (1.77 mmol, 2.0 equiv.) of HOBT. At this point 457 mg, 577 μL (25.2 mmol, 4.0 equiv.) is added via syringe over 5 minutes. The reaction is allowed to stir at room temperature for 18 hrs, then is concentrated on a rotary evaporator under high vacuum in order to remove the DMF. The residue is triturated with methanol and the crude solids are recovered by filtration. These residues are then purified by flash chromatography using a gradient of 5-10% methanol in methylene chloride as eluent. The eluted material, which is obtained from chromatography, is concentrated, dried under high vacuum, suspended in methylene chloride, dried over K2CO3, concentrated, then crystallized from methanol to give the free base of the pure product as 345 mg (79%) of a yellow solid. Mass Spec.: calc. for [C27H32FN4O5+H]+ Theor. m/z=393; Obs.=393.

1. customInto a 100 mL round bottom flask equipped with a nitrogen inlet and magnetic stirrer
2. additionAt this point 457 mg, 577 μL (25.2 mmol, 4.0 equiv.) is added via syringe over 5 minutes
3. concentrationis concentrated on a rotary evaporator under high vacuum in order
4. customto remove the DMF
5. customThe residue is triturated with methanol
6. filtrationthe crude solids are recovered by filtration
7. customThese residues are then purified by flash chromatography
8. customThe eluted material, which is obtained from chromatography
9. concentrationis concentrated
10. customdried under high vacuum
11. dry with materialdried over K2CO3
12. concentrationconcentrated
13. customcrystallized from methanol